DESCRIPTION (Taken in part from applicant's abstract) Diabetic nephropathy is the most common cause of kidney failure in the United States, particularly for those individuals with type I diabetes (IDDM). It is known that the risk of diabetic nephropathy is enhanced by poor glucose control and that this factor explains only in part the potential for developing nephropathy. Moreover, control of hypoglycemia is extremely difficult to accomplish over the lifetime of the diabetic patient. Several lines of evidence indicate that the renin-angiotensin system may influence the progress of established diabetic nephropathy. The aim of the present study is to determine whether treatment of an earlier stage of diabetes can slow or stop development of diabetic structural changes in the kidney. The long-term objective is to prevent diabetic nephropathy from developing. The clinical trial will focus on normotensive patients, ages 16 to 35 with two to 20 years of type I diabetes and without significant renal functional abnormalities. The subjects will be randomized initially into a parallel, double-blind, placebo-control study involving three groups of subjects with 85 individuals per group. The first group will be a placebo group. The second group will receive an angiotensin converting enzyme (ACE) inhibitor, Enalapril. The third group will receive an angiotensin receptor blocker, Losartan. The patients will have no particular intervention to maximize glucose control, as they will follow their usual diabetes management. The baseline studies will include measurements of glomerular filtration rate (GFR), urinary albumin excretory (UAE) rate, blood pressure (BP), and a renal biopsy under ultrasound guidance at the beginning of the study. The patients will then be followed three times per year, and annual measurements of the filtration rate will be conducted with a second kidney biopsy after five years. The main endpoint of the study will be key kidney structural changes over time, especially in mesangial fractional volume. Secondary endpoints will include measurements of kidney function, especially urinary albumin excretory rate. The studies will determine whether renin-angiotensin system blocking in the earliest diabetic nephropathy prevents early structural changes in the kidneys of diabetic patients. The study will be carried out at the University of Minnesota Medical School, McGill University, and the University of Toronto. Through this application, funds are sought to cover costs of patients at the University of Minnesota and the renal structural and functional studies performed at the Minneapolis Center for all participating centers. Support for other costs is being sought from the Medical Research Council of Canada, with additional support from Merck, Inc. USA.